August 5th, 2012
PPIs: Are the risk issues being overplayed?
I have been using PPIs to manage GERD and acid-sensitive dyspepsia since omeprazole first became available in 1989. Although no drug class is absolutely safe, there is, as yet, not a single case report of a death related to this drug class, despite hundreds of millions of patient-years of exposure. Despite this remarkable safety profile, much attention has focused recently on the overall safety of PPIs, as they have been associated with enteric infections (e.g., c. difficile), decreased bone density, electrolyte abnormalities (e.g., low magnesium), etc. However, most of these risks have been described in epidemiological studies that can establish association but not causation, and we learned an important lesson about interpreting such results with caution after authors and the FDA sent a message about the so-called interaction between PPIs and clopidogrel that turned out to be clinically irrelevant.
Despite the benefits of PPIs, increased scrutiny of the safety of this drug class has led a number of my patients to question recommendations about trying or continuing PPI therapy. I think that patients are wise to ask about the relevant side effects of any drug, but I have had trouble giving much in the way of advice or information about PPI risks, given the lack of credible evidence of cause and effect.
So, what do you tell your patients about risks when you start them on a PPI therapy?
What do you tell patients on long-term PPI therapy?
Do you use drug holidays?
Do you do bone-density studies earlier or more often in patients on PPIs?
Do you monitor magnesium levels?
Do you have patients stop therapy if they at risk for enteric infections (e.g., from hospital antibiotic exposure, travel to developing nations, etc.)?
I am looking forward to your insightful comments.
5 Responses to “PPIs: Are the risk issues being overplayed?”
M. Brian Fennerty, MD
Editor-in-Chief
NEJM Journal Watch Gastroenterology
Biography | Disclosures | Summaries
Learn more about Gut Check on Gastroenterology.
NEJM Resident 360 Curbside Consults Podcast- How the Pediatric Boards Are Made with Dr. Andrew Dwyer
- Global Health, GLocal Health, and the Indian Health Service with Dr. Adriann Begay
- Immune Checkpoint Inhibitors with Dr. Kerry Reynolds
- Management of Acute Coronary Syndrome in Older Adults with Dr. Abdulla Damluji
- Culinary Medicine with Dr. Jaclyn Albin and Milette Siler, RD
While I agree with you that PPIs have generally a good safety profile compared to other drug classes, I think they are often overused. I am a pharmacist, so I’m constantly looking closely at patients’ medication lists for unnecessary drug therapy. Often, these patients are continued on PPIs for hospital stays and often do not realize what it is being used for. I think a bigger issue than the safety profile of PPIs is the overuse of PPIs. It’s an extra pill, an extra burden on the patient and the healthcare system. When discontinuing, however, I do taper down the dose to avoid rebound symptoms.
As for the osteoporosis prevention, I follow the same guidelines for osteoporosis prevention as patients not on PPIs, but I supplement calcium citrate to attain better absorption of calcium.
I’d be interested to read other responses about the infection and magnesium issues.
While PPIs are great at what they do, I am not a fan for many reasons. My main concerns with PPIs do not stem from the list of possible risk lised above, but rather from the overuse of this medication without a clinical indication for it, which leads to dependence. It has been shown that reducing acid production with a PPI causes an increase in gastrin production. This in turn leads to an increase in proton pumps in the stomach which results in increased dosing requirements for some patients (upwards of 40mg BID dosing). Patients that do not need long term treatment with a PPI, but for some reason remain on these medications (possibly post hospitalization), find it difficult to stop the medication due to rebound reflux which often times is worse than prior to starting treatment.
Long term PPI patients with uncomplicated GERD or NUD have a choice. I explain that they can either liver with their symptoms trying as best as they can with diet and lifestyle modification or they can take a PPI and accept that there is a possible, as yet unproven but almost certainly, at worst, low risk of having one of the adverse effects that have been proposed.
I do encourage patients with uncomplicated GERD/NUD to try periodically without their PPI.
I do not monitor Mg levels
I do try to stop PPIs in inpatients unless they have a strong indication for treatment because of C. diff
If patients require long term PPI’s, I try to use the lowest dose that controls their symptoms. I will often go to an every other day regimen in the hope that the “day off” may lower the risk of some of the side effects.
I will explain to the patients the risks. I will often add a low dose Ca/Mag tablet, but rarely order a bone density.
I always try to give patients a historical perspective on treatment of reflux. Emphasize lifestyle efforts, (smaller meals, less alcohol and caffeine, and save the ppi’s for when nothing else works.